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e:Med Meeting 2017

on Systems Medicine

November 21 - 23, 2017

Alte Mensa, University of Göttingen

Table of Contents Organisation 4

Scientific Program Committee 4 Welcome Remarks by Prof. Dr. Tanja Zeller and Prof. Dr. Karsten Rippe 5 e:Med Project Committee 6 Conference Management 7 General Information & Floor Plan 8 Program 13

Speakers 19 Oral Presentations 41 Overview 43 Oral Abstracts according to Time Schedule 47

Satellite Symposium on Technological Innovations 47 Systems Medicine Visionary Talk 55 Technologies in Systems Medicine 59 Systems Medicine in European Context 67 Systems Medicine of Diseases 73 Modelling in Systems Medicine 81 Datenschutzgrundverordnung 89 Systems Medicine Impulse Talks 93 Systems Medicine Approaches in Clinics 99

Poster Presentations 111 Overview Flash Talks 111 Overview Poster 115 Poster Abstracts 127 Technologies in Systems Medicine 127 Systems Medicine of Diseases 143 Modelling in Systems Medicine 193 Systems Medicine Approaches in Clinics 241 Exhibitors 261

Company Lunch Talks 261 Exhibition Stands 267

e:Med 275 Project Groups 275 List of e:Med Systems Medicine Research Consortia 281 List of e:Med Demonstrators for an Individualized Medicine 297 List of e:Med Junior Research Groups 305 List of e:Med Junior Research Alliances 307

Alphabetical List of Participants 315 Imprint 326

Scientific Program Committee Organisation

Scientific Program Committee

Prof. Dr. Nina Babel Division of Nephrology and Internal Intensive Care Medicine, Charité Berlin

Prof. Dr. Friedrich Feuerhake Institute for Pathology, Hannover Medical School

Dr. Roberto Goya-Maldonado Systems Neuroscience and Imaging in Psychiatry, University Medical Center, Göttingen

Dr. Frank Kramer Department of Medical Statistics, University Medical Center, Göttingen

Prof. Dr. Markus Löffler Institute for Medical Informatics, Statistics and Epidemiology (IMISE), Leipzig University

Prof. Dr. Markus Nöthen Institute of Human Genetics, University Hospital Bonn

Prof. Dr. Karsten Rippe German Cancer Research Center (DKFZ), BioQuant Heidelberg

Prof. Dr. Philip Rosenstiel Institute of Clinical Molecular Biology (IKMB), CAU Kiel, UKSH

Prof. Dr. Tanja Zeller University Medical Center Hamburg-Eppendorf, Hamburg

4 e:Med Meeting 2017 on Systems Medicine, Alte Mensa Göttingen

Organisation Welcome Remarks 2017

Welcome Remarks 2017

It is a great pleasure to cordially welcome you all on behalf of the e:Med Project Committee and the local organizers at the 4th e:Med Meeting 2017 on Systems Medicine held November 21 – 23 at the bright and delightful “Alte Mensa” in Göttingen.

We are very much looking forward to a stimulating three-day conference program featuring 17 keynote lectures by invited international speakers, 17 short talks by e:Med experts, 22 poster flash talks, 4 company sessions and a poster exhibition with more than 120 posters reflecting the active e:Med community. The top three posters will be honored with the e:Med 2017 Poster Award. The conference opens with a satellite workshop on technical innovations, organized by the e:Med project group epigenetics & sequencing. A special highlight is the evening event “Karriere in der Systemmedizin” with public talks for young investigators and systems medicine “unplugged” by Uri Alon.

Outstanding experts in the interdisciplinary field of systems medicine will inspire us with presentations on state-of-the-art research and the latest developments from e:Med projects and beyond. The program covers important topics from technologies and models in systems medicine to causes and courses of diseases and concludes with the translation into the clinics. Sessions on European systems medicine as well as systems medicine impulse talks inform on international and overarching projects. Moreover, recent technological developments are on display in company lectures and the industrial exhibition of our sponsors. You are cordially invited to actively participate in meetings and presentations of all e:Med project groups. Take a look at the program to find the diverse activities throughout the conference and join the discussions with other experts in your field of interest.

The e:Med annual meeting would not be feasible without the help of our supporters: First and foremost we are very grateful to the BMBF for funding the e:Med program. In addition, the generous support of our company sponsors allows us to have the get together on Tuesday 21st and the conference dinner on Wednesday 22nd with live music at the historic restaurant Bullerjahn.

Take the opportunity to meet your e:Med colleagues and actively engage in the discussions on the many aspects of systems medicine in the unique atmosphere of the renowned university town Göttingen.

Professor Dr. Tanja Zeller Professor Dr. Karsten Rippe Speakers of the e:Med project committee

e:Med Meeting 2017 on Systems Medicine, Alte Mensa Göttingen 5

e:Med Project Committee Organisation

Members of the e:Med Project Committee Prof. Dr. Nina Babel, Charité Berlin Prof. Dr. Friedrich Feuerhake, Hannover Medical School Dr. Roberto Goya-Maldonado, Georg August University Göttingen Prof. Dr. Steffen Just, University Hospital Ulm Dr. Frank Kramer, Georg August University Göttingen Prof. Dr. Dagmar Kulms, University Hospital Carl Gustav Carus, Dresden Prof. Dr. Peter Lichter, German Cancer Research Center (DKFZ), Heidelberg Prof. Dr. Markus Löffler, Leipzig University Prof. Dr. Markus Nöthen, University of Bonn Prof. Dr. Ingo Röder, Technische Universität Dresden Prof. Dr. Philip Rosenstiel, University Hospital Schleswig-Holstein, Kiel Prof. Dr. Martin Sos, University Hospital of Cologne Prof. Dr. Rainer Spang, Universität Regensburg Prof. Dr. Roman Thomas, University of Cologne Prof. Dr. Tanja Zeller, University Medical Center Hamburg-Eppendorf, Hamburg Dr. Michael Ziller, Max Planck Institute of Psychiatry, München


Organisation Conference Management

Conference Management e:Med Management Office c/o German Cancer Research Center, DKFZ Im Neuenheimer Feld 581, V025 D-69120 Heidelberg Fax: +49 (0)6221 42 46 51 Dr. Silke Argo E-Mail: [email protected] Phone: +49-6221-424743

Dr. Lioba Courth E-Mail: [email protected] Phone: +49-6221-424748

Dr. Karin Greulich-Bode E-Mail: [email protected] Phone: +49-6221-424767

Dr. Tanja Jutzi E-Mail: [email protected] Phone: +49-6221-424742

Iris Nath E-Mail: [email protected] Phone: +49-6221-424649 Local organisation

Dr. Roberto Goya-Maldonado Maria Keil Systems Neuroscience and Imaging in Psychiatry University Medical Center Goettingen Georg-August-University Goettingen

Prof. Dr. Tim Beißbarth Dr. Frank Kramer Department of Medical Statistics University Medical Center Goettingen Georg-August-University Goettingen

Prof. Dr. Ulrich Sax Department of Medical Informatics University Medical Center Goettingen Georg-August-University Goettingen


mailto:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]

General information Organisation

Oral Presentations

The time slots for oral presentations are as follows - please prepare your presentation accordingly and strictly respect the time limits:

Keynote Speaker 25 min talk + 5 min discussion

Short Talk 12 min talk + 3 min discussion

Slide desk

Please hand in your slides for presentation on an USB stick at the Slide Desk in the lecture hall latest until the session before your presentation. A Windows PC is available for Powerpoint presentations. To ensure an efficient course of the sessions, we can allow the use of your own computer only in exceptional cases, e.g. if you need a special program to present a movie embedded in your presentation. All presentation files will be deleted after the conference.

Poster Presentations

Each poster has been assigned an abstract number listed in this book beginning page 111. Posters will be discussed in the poster exhibition as follows: Poster Session I Odd numbers Tuesday, November 21, 05.00 – 06.30 pm Poster Session II: Even numbers Wednesday, November 22, 05.30 – 07.00 pm During this time, the presenting author is expected at the poster in order to present the data. Please note:

• Posters may be set-up November 21, 2017, from 10.00 am to 1.30 pm. • Poster pins/strips to fix your poster will be provided on tables at exhibition site. • Posters may be removed at the end of the conference. Remaining posters can not

be sent.


Organisation General information

e:Med Poster Award 2017

All posters will be evaluated by the program committee panel and the top three posters will be awarded € 150 each. The ceremony is scheduled for Thursday, November 23, 2017 around 3:30 pm. Award criteria:

• scientific quality and novelty • concise statement of significance of research • focused problems, innovative solutions • succinct, clear, engaging presentation • visual balance between text, figures and tables

Important The Poster Award will only be allocated to participants who are present at the award ceremony or who have nominated a representative who will present their poster.

Internet Connection - WLAN Access

WLAN access is available during the conference via eduroam. To alternatively use an open guest network, please please ask at the registration desk for WLAN Code.

Evening Networking Events

• Get together with wine & snacks at the venue on Tuesday, November 21. • Dinner at the restaurant Bullerjahn on Wednesday, November 22 starting from 7:30

pm. The restaurant is located in the old townhall of Göttingen (Markt 9, http://www.bullerjahn.info). Enjoy the historic atmosphere of the vaulted cellar with nice food followed accompanied with electronic music by Maewen Forest (https://soundcloud.com/maewenmusic). Dinner is offered for free, drinks are asked to be paid by each participant. Please note that you need to be registered to join this event.

Cell Phones

Please turn off your cell phone during all sessions!

Photography

It is strictly forbidden to take pictures of any scientific data. We encourage participants to share their unpublished data, hence, do not photograph any posters or slides.


http://www.bullerjahn.info/https://soundcloud.com/maewenmusic

Floor Plan Organisation

Venue: Ground floor


Organisation Floor Plan

Venue: First floor


Organisation Program

Tuesday, November 21, 2017

10:00 - 11:00 am Breakout Project Group: PG 1 Informatics & Modelling Chair PG 1: Matthias Ganzinger

11:00 - 01:00 am Satellite Symposium: Technological Innovations Organized by Project group Epigenetics & Sequencing Chair: Philip Rosenstiel, Friedrich Feuerhake, Karsten Rippe 11:00 - 11:30 am Angela Vasaturo, INSERM, Paris

Unraveling the tumor microenvironment architecture by multispectral imaging

11:30 - 12:00 pm Philipp Mallm, DKFZ Heidelberg Follow response to treatment by single-cell sequencing 12:00 - 12:30 pm Andreas Schlitzer, University of Bonn Unravelling Cellular heterogeneity - A single cell biology approach 12:30 - 01:00 pm Stefan Günther, MPI Bad Nauenheim High resolution single cell analysis in complex adult tissues

01:00 - 01:45 pm Registration & Welcome Supper 01:45 - 02:00 pm Welcome Address Tanja Zeller, Spokesperson e:Med Project Committee Blanche Schwappach, UMG/Uni Göttingen Johannes Mohr, Bundesministerium für Bildung und Forschung 02:00 - 02:45 pm Uri Alon, Weizmann Institute, Israel

Visionary talk: Design principles of circuits for tissue homeostasis

02:45 - 04:00 pm Technologies in Systems Medicine Chair: Philip Rosenstiel, Frank Kramer 02:45 - 03:15 pm Benno Schwikowski, Institut Pasteur Keynote: LEAN analysis biological network hot spots in the age of Big Data 03:15 - 03:30 pm Wolfram Gronwald, University of Regensburg Metabolomic Changes in Lymphoma in Response to Stromal Stimuli 03:30 - 03:45 pm Katharina Nekolla, Definiens AG, Munich

Spatial organization of B cells and T cells predicts loss of renal transplant function

03:45 - 04:00 pm Chris Lawerenz, DKFZ Heidelberg Introducing the de.NBI Cloud – the novel compute and storage infrastructure for life sciences

04:00 - 04:30 pm Coffee Break

04:30 - 06:30 pm Poster Session I (odd numbers) Chair: Ingo Röder 04:30 - 05:00 pm Poster Flash Talks (11 talks à 3 min) 05:00 - 06:30 pm Poster Exhibition

06:30- 07:45 pm Karriere in der Systemmedizin: Public session for young investigators (English/Deutsch)

Moderation: Friedrich Feuerhake Roberto Goya-Maldonado Wie lebt der Arzt die Systemmedizin? Frank Kramer Als Informatiker in der Systemmedizin Antje Walz Karriere in der Industrie Markus Nöthen Perspektive des Senior Scientists Uri Alon Systems Medicine "unplugged"

07:45 - 10:00 pm Get Together with Wine & Snacks - Networking at Venue


Program Organisation

Wednesday, November 22, 2017

08:30 - 09:00 am Morning Coffee 09:00 - 10:30 am Systems Medicine in European Context Chair: Peter Lichter, Karsten Rippe 09:00 - 09:30 am Philip Rosenstiel, University of Kiel SYSCID – A systems medicine approach to chronic inflammatory 09:30 - 10:00 am Bernd Pichler, University of Tübingen German imaging science in European context 10:00 - 10:30 am Markus Löffler, University of Leipzig Medical Informatics Initiative and Systems Medicine Initiative

10:30 - 11:00 am Coffee Break

11:00 - 12:30 pm Systems Medicine of Diseases Chair: Roberto Goya-Maldonado, Dagmar Kulms 11:00 - 11:30 am Conor Liston, Weill Cornell Medical College, NYC

Keynote: Frontostriatal mechanisms of anhedonia in novel neurophysiological subtypes of depression

11:30 - 11:45 am Julia Krause, University Medical Center Hamburg-Eppendorf, DZHK Metabolomics in Translational Medicine – A Link between Acylcarnitines and Atrial Fibrillation

11:45 - 12:00 pm Nima Abedpour, University of Cologne Reconstruction of tumor evolution from massively parallel sequencing data 12:00 - 12:15 pm Elisa Espinet, HI-STEM & DKFZ

Transcriptomic landscape of Pancreatic Cancer and normal Epithelial and Stromal cells directly isolated from human samples reveals common and cell-type specific deregulated nodes

12:15 - 12:30 pm Vicente Yépez, TU Munich Multi-omics analysis methods for the genetic diagnosis of rare diseases

12:30 - 02:30 pm Lunch Break

01:00 - 02:10 pm Company Lunch Talks 01:00 - 01:30 pm Martin Lundberg, Olink Proteomics:

A precision proteomics solution for targeted human protein biomarker discovery

01:40 - 02:10 pm Ingolf Cascorbi, UKSH for HMG Systems Engineering HMG Systems Engineering: Clinical Implementation of Pharmacogenetics


Organisation Program

Wednesday, November 22, 2017 continued

02:30 - 04:00 pm Modelling in systems medicine Chair: Friedrich Feuerhake, Markus Löffler 02:30 - 03:00 pm Antje Walz, Roche Basel Keynote: From Ideas to Medicine – with Modelling and Simulation 03:00 - 03:15 pm Dagmar Kulms,TU Dresden

Predicting sensitivity of malignant melanoma to combination therapies by network modeling

03:15 - 03:30 pm Peter-Martin Bruch, University Hospital Heidelberg A drug - cytokine interaction map for lympho-proliferative disorders 03:30 - 03:45 pm Kathrin Thedieck, University Medical Center Groningen & University

Oldenburg Computational modelling of amino acid signaling to kinase networks

03:45- 04:00 pm Verena Körber, DKFZ Heidelberg Clonal evolution in adult glioblastoma

04:00 - 04:30 pm Coffee Break

04:30 - 05:00 pm Datenschutzgrundverordnung Organized by Project group Data security & Ethics Chair: Christoph Schickhardt 04:30 - 05:00 pm Boris Reibach, University of Oldenburg Der neue EU-Datenschutz: Folgen für die Forschung

05:00 - 07:00 pm Poster Session II (even numbers) Chair: Tanja Zeller 05:00 - 05:30 pm Poster Flash Talks (11 talks à 3 min) 05:30 - 07:00 pm Poster Exhibition

06:45 - 07:30 pm Breakout Project Groups PG 2: Data security & Ethics Room Adam-von-Trott Chair PG 2: Christoph Schickhardt

PG 3: Image processing Taberna Chair PG 3: Bernd Pichler

07:30 - 11:00 pm e:Med Dinner & Party Göttingen Restaurant Bullerjahn


Program Organisation

Thursday, November 23, 2017

08:30 - 09:00 am Morning Coffee

09:00 - 10:30 am Systems Medicine Impulse Talks Chair: Ingo Röder, Michael Ziller 09:00 - 09:30 am Oliver Kohlbacher, University of Tuebingen (iD:Sem)

Closing the translational gap – integrating of high-throughput data for personalized cancer treatments into clinical processes

09:30 - 10:00 am Peter Jansen, AMC Amsterdam (LiSyM) Progressive fibrosis as driving force behind liver cirrhosis, liver failure and hepatocellular carcinoma

10:00 - 10:30 am Alfred Pühler, University of Bielefeld (de.NBI) The German Network for Bioinformatics Infrastructure de.NBI Helps to Handle Big Data in Life Sciences

10:30 - 11:00 am Coffee Break

11:00 - 12:30 pm Sytems Medicine Approaches in Clinics I Chair: Markus Nöthen, Nina Babel 11:00 - 11:30 am Erwin Böttinger, HPI & University of Potsdam

Keynote: Translational approaches for progressive diseases 11:30 - 11:45 am Sylvane Desrivières, King’s College London, United Kingdom

Updates on the ENIGMA-Epigenetics Working Group 11:45 - 12:00 pm Ateequr Rehman, Christian-Albrechts-University Kiel

Anti-TNFα restores disrupted metabolic interaction of the intestinal microbiome in IBD

12:00 - 12:15 pm Nina Babel, Charité – Universitätsmedizin Berlin Multi-omics based strategy to predict graft function and personalize immunosuppressive therapy in kidney transplantation

12:15 - 02:15 pm Lunch Break

12:50 - 01:55 pm Company Lunch Talks 12:50 - 01:20 pm Karsten Rippe, DKFZ and Matthias Prucha, Illumina Illumina: Experiences from the 2017 e:Med Summer School

How advancements in Next Generation Sequencing support Functional Genomics Research

01:25 - 01:55 pm Lukas Paul, Lexogen GmbH Lexogen: Gene Expression Profiling of Blood Samples: QuantSeq 3’ mRNA-Seq Library Preparation with Globin Reduction

02:15 - 03:30 pm Sytems Medicine Approaches in Clinics II Chair: Tanja Zeller, Roman Thomas 02:15- 02:45 pm Julia Stingl, University of Bonn

Keynote: Pharmacogenomics: from translational research to next generation benefit-risk evaluation

02:45 - 03:00 pm Mathew Divine, University of Tübingen Integrating multi-omics and multi-modality medical imaging to assess hepatocellular carcinoma patient outcome under Sorafenib treatment: A progress report of the Multiscale HCC project

03:00 - 03:15 pm Ingo Roeder, TU Dresden “Systems hematology” – Opportunities, benefits, and limitations 03:15 - 03:30 pm Tim Beißbarth, University Medical Center Göttingen

How to report somatic variants in molecular tumor boards

03:30 - 03:45 pm e:Med Poster Award Ceremony and Closing Remarks Moderation: Karsten Rippe, Roberto Goya-Maldonado Karsten Rippe, Spokesperson e:Med Project Committee 03:45 - 04:15 pm Coffee & Snacks


Speakers


Tue Nov 21 Satellite Symposium on technological innovations 11:00 ‐ 11:30 am Unraveling the tumor microenvironment architecture by

multispectral imaging Angela Vasaturo

Dr. Angela Vasaturo is a Senior Researcher in the field of Tumor Immunology in the Integrative Cancer Immunology at the Cordeliers Research Center in Paris, France. Dr. Vasaturo was trained as a Medical Biotechnologist and pursued a Ph.D. degree in Chemical Engineering (both at University of Naples “Federico II”, Naples, Italy). She’s been working as Post‐doctoral researcher at the NCMLS in the years 2010‐2015, being the recipient of an EMBO short‐term fellowship, amongst others. She joined Dr. Jerome Galon’s Laboratory of Integrative Cancer Immunology at the Cordeliers Research Center in 2015. Dr Vasaturo has a sound knowledge on a broad range of in vivo and in vitro skills, and has a keen interest in microscopy and state‐of‐the‐art imaging techniques, including Multispectral Imaging. Dr. Vasaturo has published 16 papers in top‐tier scientific journals, delivered seminars and tutorials internationally and carried out multiple collaborations in the field.

11:30 ‐ 12:00 pm Follow response to treatment by single‐cell sequencing Jan‐Philipp Mallm

Jan‐Philipp Mallm performed his PhD work in the group of Karsten Rippe at the German Cancer Research Center (DKFZ, Heidelberg). Here he studied chromatin feedback on telomere maintenance in embryonic stem cells and on DNA repair in cancer initiating cells. During his postdoc he exploited epigenetic deregulation in chronic lymphocytic leukemia (CLL) revealing a transcription factor network controlling the disease phenotype. Since 2015 he heads the Chromatin and RNA methods (CHARM) lab within the Heidelberg Center for Personalized Oncology (HIPO) establishing (single‐cell) sequencing readouts for primary tumor samples. In addition, in 2017 he started as a Team Leader for dissecting cellular heterogeneity in leukemic patients by single‐cell sequencing approaches in the division of Karsten Rippe.


Tue Nov 21 Satellite Symposium on technological innovations 12:00 ‐ 12:30 pm Unravelling Cellular heterogeneity ‐ A single cell biology approach Andreas Schlitzer

After his studies in Marburg and Manchester, Andreas Schlitzer did his PhD at the Technical University of Munich with a focus on dendritic cells. After his PhD he moved to the lab of Florent Ginhoux, Singapore Immunology Network, Singapore were he investigated how the functional polarization of myeloid cells is enforced using various single cell biology approaches, such as single cell transcriptomics, high dimensional flow cytometry and mass cytometry. Since 2016 he is an Emmy Noether Group leader at the Life & Medical Sciences Institute of the University of Bonn and employs an integrated single cell biology approach to identify the molecular mechanisms guarding myeloid cell differentiation and functional polarization during inflammation.

12:30 ‐ 01:00 pm High resolution single cell analysis in complex adult tissues Stefan Günther

Stefan Günther is currently the head of the next‐generation core facility, Bioinformatics and Deep Sequencing Platform at the Max‐Planck‐Institute for Heart‐ and Lung Research in Bad Nauheim. He studied biology at the Martin‐Luther University Halle‐Wittenberg, where he received his Diploma in 2002. For his PhD, he joined the MPI for Heart‐and Lung research. There he investigated muscle‐specific transcription factors. From 2009 ‐ 2013 he was a postdoctoral research fellow at the department of cardiac development and remodeling with Prof. Dr. Thomas Braun with focus on muscle stem cells. Dr. Günther is co‐author of numerous publications in the area of nucleic acid research and single‐cell sequencing.


Tue Nov 21 Welcome Remarks 01:45 ‐ 01:50 pm Tanja Zeller, Speaker e:Med Project Comittee

Professor Dr. Tanja Zeller is spokesperson of the e:Med project committee and professor for Genomics and Systems Biology at the University Heart Center Hamburg. She is head of the e:Med junior research alliance symAtrial. In her research, she investigates the molecular mechanisms of atrial fibrillation and additional cardiovascular diseases with the aim to identify genes and signaling pathways contributing to disease.

01:50 ‐ 01:55 pm Blanche Schwappach, UMG/Uni Göttingen

Professor Dr. Blanche Schwappach is research dean of the University Medical Center Göttingen and head of the department of molecular biology. She received her PhD from the University Hamburg in 1996. After working as a scientist in San Franciso, Heidelberg and Manchester, she joined the University of Göttingen in 2010 where she became Professor and Director of the Department of Molecular Biology. Her research focus is membrane protein biogenesis in different physiological conditions.

01:55 ‐ 02:00 pm Johannes Mohr, BMBF

Dr. Johannes Mohr is assistant head of division 614, Development of Methods and Structures in the Life Sciences, at the Federal Ministry of Education and Research (BMBF) since 2016. Dr. Mohr studied physics and received his PhD from the Technical University of Berlin.


Tue Nov 21 Systems Medicine Visionary Talk 02:00 ‐ 02:45 pm Design principles of circuits for tissue homeostasis Uri Alon

Born in Tel Aviv, Israel, Prof. Uri Alon earned his BSc in physics and mathematics, and his MSc in physics from the Hebrew University of Jerusalem (1989). He was awarded his PhD in physics from the Weizmann Institute of Science (1996), and was a postdoctoral fellow in experimental biology in the Departments of Physics and Molecular Biology at Princeton University (1997‐1999), before taking a position at the Weizmann Institute in 1999. He is the incumbent of the Abisch‐Frenkel Professorial Chair. Prof. Alon works at the interface between physics and biology, and is one of the founders of the field of systems biology. Prof. Alon has made influential discoveries, chief among them that biological networks are made of repeating circuit patterns called network motifs. His team includes physicists and biologists working together to understand the principles of the molecular systems that guide the decisions of our bodies’ cells. He is currently developing cocktails of drugs to combat cancer at low doses that avoid side effects, defining the design principles for hormone circuits and their susceptibility to aging and diseases such as type 2 diabetes, neurodegeneration and depression. He also studies principles of human behavior using concepts from theater and accurate physics measurements and mathematical models. Prof. Alon received the 2014 Nakasone prize awarded by the Human Frontiers Science Project for a breakthrough in the life sciences for his work on network motifs and the Jacques Solvay Chair in Physics in 2017. He was awarded the Michael Bruno Memorial Award in 2009 from the Yad Hanadiv Foundation. His previous prizes and honors include: the Moore Fellowship, California Institute of Technology (2000), EMBO Young Investigator Award (2001), Minerva Junior Research Group on Biological Computation (2003), Morris L. Levinson Award in Biology of the Weizmann Institute’s Scientific Council (2003), IBM Faculty Award (2003), the Overton Prize of the International Society for Computational Biology (2004). Prof. Alon is an enthusiastic father of three daughters, Gefen, Tamar, and Carmel. He acts and teaches in Playback Theatre, an improvisation theatre that aims to connect people by listening to real life stories told by audience members and enacting them on the spot. Uri is an outspoken advocate of the importance of good human relationships in science, as seen on his 2013 TED talk.


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Wed Nov 22 Systems medicine in the European context 09:00 ‐ 09:30 am SYSCID – A systems medicine approach to chronic inflammatory

diseases Philip Rosenstiel

Philip Rosenstiel is head‐member of the Institute of Clinical Molecular Biology at Kiel University and University Hospital Schleswig Holstein. He holds a professorship in Molecular and Evolutionary Medicine. He studied medicine in Kiel and Boston. He received his MD degree on the characterization of Angiotensin II as a neurotrophic factor in 2003. His main scientific interest is to contribute to an understanding of the complex interactions between human intestinal mucosa and the environment in health and disease. Emphasis is given to the translation of positional genetic signals in inflammatory bowel disease into distinct, functional molecular effects in underlying cellular pathways and networks. He also develops novel tools and techniques using large‐scale sequencing and bioinformatics to understand regulatory events and cellular/bacterial response profiles in model systems of chronic inflammatory diseases. He serves as coordinator of several large‐scale research initiatives in human diseases (e.g. BMBF SysINFLAME, H2020 SYSCID).

09:30 ‐ 10:00 am German imaging science in European context Bernd Pichler

Prof. Dr. Bernd Pichler is director of the Werner Siemens Imaging Center and chair of the Department of Preclinical Imaging and Radiopharmacy, Clinic of Radiology, University of Tübingen, Germany. He earned his PhD in physics at the Department of Nuclear Medicine, Technical University of Munich, in 2002 and subsequently worked at the Department of Biomedical Engineering, University of California, Davis, USA. In 2005 Bernd Pichler became head of the Laboratory for Preclinical Imaging and Imaging Technology at the University of Tübingen. In December 2007, Dr. Pichler accepted the call of the University of Tübingen for a full (W3) professorship in “Preclinical Imaging and Imaging Technology”. In 2008 he became head of the Radiopharmacy and in 2011 both, the Laboratory for Preclinical Imaging of the Werner Siemens‐Foundation and the Radiopharmacy joined, to become the Department of Preclinical Imaging and Radiopharmacy, with Prof. Pichler as director and chair of the department. His work includes multi‐modality imaging in oncology, immunology and neurology as well as the development of new imaging technologies and innovative imaging probes.

© Dr. Tebke Böschen Uni Kiel


Wed Nov 22 Systems medicine in the European context

10:00 ‐ 10:30 am Medical Informatics Initiative and Systems Medicine Initiative Markus Löffler

Dr. Markus Löffler is Professor and Director of the Institute of Medical Informatics, Statistics and Epidemiology in Leipzig. He is the acting director of the Center of Clinical Trials Leipzig, scientific director of the Interdisciplinary Center for Bioinformatics, as well as the director of the LIFE Research Center for Civilisation Diseases. He is originally trained as a physicist and medical doctor and was promoted as a professor in medical documentation, statistics and biomathematics from the University of Cologne. In 1994 he became a full Professor and head of the Institute at the University of Leipzig. His research interests include clinical trials and cohort studies for molecular markers, bioinformatics, systems biology models as well as medical statistics and epidemiology. Dr. Löffler has an h‐index of 87 and published numerous publications with far more than 30.000 citations.

Wed Nov 22 Systems Medicine of Diseases 11:00 ‐ 11:30 am Keynote: Frontostriatal mechanisms of anhedonia in novel

neurophysiological subtypes of depression Conor Liston

Conor Liston is an Assistant Professor of Neuroscience and Psychiatry at the Feil Family Brand and Mine Research Institute and Department of Psychiatry at Weill Cornell Medicine. He studied Medicine and Neuroscience at Harvard and Weill Cornell Medical College and received his PhD from the Rockefeller University. After postdoctoral research at New York University and at Stanford, he became an Assistant Professor of Neuroscience at Weill Cornell in 2014. His research seeks to identify prefrontal circuit mechanisms supporting learning and memory and to understand how they are disrupted in stress‐related psychiatric disorders, operating at the interface between systems neuroscience and biological psychiatry.


Wed Nov 22 Systems Medicine of Diseases 11:30 ‐ 11:45 am Metabolomics in Translational Medicine – A Link between

Acylcarnitines and Atrial Fibrillation Julia Krause

Julia Krause is a PhD student in the group of Molecular Cardiology, Genomics and Systems Biology at the University Heart Center Hamburg, Germany. She graduated in 2015 in Molecular Medicine at the Friedrich‐Schiller‐University Jena, Germany. Her PhD thesis is embedded in the multi‐disciplinary e:Med symAtrial consortium and aims to identify and characterize atrial fibrillation‐related genes, respective pathways and their functional assessment. Closely working together with clinicians, bioinformaticians and epidemiologists, multiple –omics data ranging from genomics, transcriptomics, miRNAs, to proteomics and metabolomics in atrial tissue and blood‐based samples, are generated and bioinformatically integrated. The findings of these ‐omics analyses are investigated and the molecular role of identified candidates is further characterize by using different molecular experimental approaches and cell models.

11:45 ‐ 12:00 pm Reconstruction of tumor evolution from massively parallel

sequencing data Nima Abedpour

Nima is currently a postdoctoral researcher at department of translational genomics at the university of Cologne. He is considered as an interdisciplinary scientist working at the interface between Physics, Information Technology and Biology. In 2009, He received his PhD in physics in the field of complex systems at the Sharif University in Tehran. Throughout his physics education and a short postdoc after that, his work was mainly focused on statistical and computational physics. His curiosity about “the life” brought him toward biology research. In 2011, he was granted an EMBO Fellowship to study biological networks especially bacterial metabolic networks. From then on, he has been doing research in theoretical biology from different aspects. Currently he is focused on cancer genomics research. His research has benefited from machine learning approaches and statistical and mathematical modeling.


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Wed Nov 22 Modelling in Systems Medicine 03:15 ‐ 03:30 pm A drug ‐ cytokine interaction map for lympho‐proliferative

disorders Peter‐Martin Bruch

Peter‐Martin Bruch started medical school in 2012. He has great interest in molecular medicine and hematology‐oncology, aiming at a career as physician scientist in this medical field based on a combined clinical and scientific education. Previously he has worked in the field of oncology in multiple different settings, including the National Center for Tumor diseases. He received the Franziska Kolb foundation scholarship in May 2017, which allows him to interrupt his studies to conduct his MD thesis. His research focus is to understand the functional role of critical signaling pathways in lympho‐proliferative diseases determining the biological basis for differential response to signals provided by the microenvironment. He has designed and currently conducts a high throughput drug‐cytokine combinational perturbation screen in primary patient derived lymphoma and leukemia cells. His project is integrated in a close collaboration (SYMPATHY project) between the Heidelberg University Hospital (Sascha Dietrich), the DKFZ (Thorsten Zenz) and EMBL (Wolfgang Huber).

03:30 ‐ 03:45 pm Computational modelling of amino acid signaling to kinase networks

Kathrin Thedieck

Prof. Dr. Kathrin Thedieck joined the Universities of Oldenburg and Groningen in 2013 in the frame of the European Medical School (EMS). For more than 10 years she has been studying the kinase networks centered on phosphatidylinositide 3‐kinases (PI3K) and the mammalian target of rapamycin (mTOR). Kathrin Thedieck did her postdoctoral training with Michael N. Hall (Basel University, CH), with whom she discovered mTOR interactors that control cancer cell survival. These efforts laid the foundation for her work done at Freiburg University where she started her own lab in 2008, and extended her efforts to develop systems approaches to the PI3K/mTOR network. In the frame of the e:Med projects GlioPATH (coordinator: Dr. C. Opitz, DKFZ, Heidelberg) and MAPTor‐NET (coordinator Prof. Dr. Sers, Charite, Berlin), Thedieck and colleagues are further developing this work with emphasis on precision therapies for cancer and genetic diseases.


Wed Nov 22 Modelling in Systems Medicine 03:45‐ 04:00 pm Clonal evolution in adult glioblastoma Verena Körber

Verena Körber studied Molecular Medicine and Systems Biology at the Universities of Ulm and Heidelberg. In her Master thesis she developed mathematical models to describe the T cell immune response to vaccinia virus. She received her Master’s degree in 2015 and then started her PhD with Prof. Thomas Höfer at the German Cancer Research Center (DKFZ) in Heidelberg. Verena Körber’s research interests lie in the processes that govern cancer initiation and progression. As part of the SYS‐GLIO consortium, she studies genetic heterogeneity along with the underlying evolutionary dynamics in glioblastoma. She is also interested in the transcriptional networks governing tumor initiation from neural stem cells.

Wed Nov 22 General Data Protection Regulation 04:30 ‐ 05:00 pm General Data Protection Regulation (GDPR) and its consequences

for research Boris Reibach

‐ Fully Qualified Lawyer studies in Augsburg ‐ Master of Laws degree in Information Technology Law from Oldenburg University ‐ Previously consultant at several community law centers in Germany and New Zealand ‐ Since 2011 Attorney at Law specialising in data protection law and External Data Protection Officer for numerous companies in various industry sectors at Scheja & Partner Attorneys at Law, Bonn, Germany ‐ Since 2014 Research Assistant at Oldenburg University, specialising in data protection and IT law ‐ Regular speaker at national and international data protection conferences ‐ Certified Data Protection Officer


Thu Nov 23 Systems Medicine Impulse Talks 09:00 ‐ 09:30 am Closing the translational gap – integrating of high‐throughput data

for personalized cancer treatments into clinical processes Oliver Kohlbacher

Research in the group of Oliver Kohlbacher (Chair for Applied Bioinformatics) focuses on method development for the analysis of high‐throughput data, immunoinformatics, and structural bioinformatics. A particular focus is on the analysis of mass spectrometric data (proteomics, metaproteomics, metabolomics), for which is group has been developing open‐source software (OpenMS) for a long time. Integrating these approaches, automating analyses and bringing the resulting workflows to the clinical application has been another focus of recent years. Oliver Kohlbacher is also the director of the Quantitative Biology Center (QBiC) and a fellow of the Max Planck Institute for Developmental Biology in Tübingen.

09:30 ‐ 10:00 am Progressive fibrosis as driving force behind liver cirrhosis, liver failure and hepatocellular carcinoma

Peter Jansen

Peter Jansen is currently the program director of LiSyM, the Liver Systems Medicine research network in Germany. Peter Jansen is honorary professor at MaCSBio, the Maastricht Center for Systems Biology and he is emeritus professor of hepatology at the Universities of Amsterdam and Groningen. He studied Medicine at the University of Nijmegen and received his PhD at the Institute of Pharmacology with work on drug metabolism in 1975. For part of his scientific training he went to the Albert Einstein College of Medicine in New York (1973‐76). In 1986 he became associate professor at the AMC in Amsterdam and in 1993 he was appointed professor of hepatology and head of the department of Gastroenterology and Hepatology in the University Medical Center in Groningen, the main liver transplantation center in the Netherlands. In 2003 he returned to Amsterdam as head of the liver unit. Peter’s research is devoted to trans‐membrane ABC transport proteins, interaction between liver and intestine, FGF19‐signalling, nuclear hormone receptors and the role of bile salts in cholestatic and metabolic liver disease.


Thu Nov 23 Systems Medicine Approaches in Clinics 10:00 ‐ 10:30 am The German Network for Bioinformatics Infrastructure de.NBI

Helps to Handle Big Data in Life Sciences Alfred Pühler

A. Pühler studied Physics at the Friedrich‐Alexander University Erlangen Nürnberg, got his Ph.D. degree in Microbiology in 1971 and habilitated in 1976. From 1980 until 2008, he was head of the Chair of Genetics at Bielefeld University. He is now running a Senior Research Group at the Center for Biotechnology at Bielefeld University. His research interests are focused on genome research of industrially relevant microorganisms and cell cultures. From 1999 to 2005, A. Pühler was member of the Science Council installed by the Federal President of Germany. He is member of three Academies, the North Rhine‐Westphalian Academy of Sciences, the German Academy of Sciences Leopoldina and the National Academy of Science and Engineering (acatech). From March 2015 on, he coordinates the Germany network for Bioinformatics Infrastructure (de.NBI) funded by the BMBF. Since August 2016, he is appointed as Head of Node of ELIXIR Germany, the German node of the European Life‐Science Infrastructure for biological Information.

Tue Nov 23 Systems Medicine Approaches in Clinics 11:00 ‐ 11:30 am Keynote: Translational approaches for progressive diseases Erwin Böttinger

Professor Dr. Erwin Böttinger is Professor and Chair of Digital Health and Personalized Medicine at the joint Digital Engineering Faculty of the Hasso Plattner Institute (HPI) gGmbH and the University of Potsdam. He is the founding director of the HPI Digital Health Center. From November 2015 to July 2017 Prof. Böttinger was Chairman of the Board of the Berliner Instituts für Gesundheitsforschung/Berlin Institute of Health (BIH). Prof. Böttinger is considered an international expert in personalized medicine and digital health, in particular from his services as founding director of the Charles Bronfman Institute for Personalized Medicine at the Icahn School of Medicine at Mount Sinai in New York, USA, from 2005 to 2015.


Tue Nov 23 Systems Medicine Approaches in Clinics 11:30 ‐ 11:45 am Updates on the ENIGMA‐Epigenetics Working Group Sylvane Desrivières

Sylvane Desrivières is Reader in Genetics at the Institute of Psychiatry, Psychology & Neuroscience at King’s College London. Having earned her MSc and PhD in Molecular Biology from the University of Paris VII, she worked in outstanding institutions in Switzerland and Germany, studying how gene activity controls biological systems of increasing complexity, from individual cells and organs to the human brain. When in 2006, advances in magnetic resonance imaging (MRI) were such that measuring changes of the brain in vivo had become a reality, she took this exceptional opportunity to move her career forward, in a world leading university. Leading Genetics Working Groups in several large international consortia, she since applies her skills to discover the genetic roots of neurophychological traits that may be disrupted in individuals suffering from mental illness, including addictions. This resulted in a remarkable portfolio of discoveries, with >65 publications in the past 10 years.

11:45 ‐ 12:00 pm Anti‐TNFα restores disrupted metabolic interaction of the intestinal microbiome in IBD

Ateequr Rehman

Ateequr Rehman is working as a senior research scientist at the Institute of Clinical molecular biology, Christian Albrechts University Kiel, Germany. Combining the background of a classical microbiologist with state of the art next generation sequencing approaches, Dr. Rehman’s research focuses on the role of gut microbial communities in the pathogenesis of complex intestinal diseases, especially in inflammatory bowel disease. His projects mainly apply high throughput sequencing approaches to investigate phylogenetic and functional interplay of intestinal microbiota in the context of disease, genotype and environmental perturbations, aiming to identify microbial communities influencing host health and disease status. As part of that, he majorly contributed to the understanding of risk gene associated microbiota in inflammation. Dr Rehman has co‐authored 35 publications in peer reviewed journals, including the journals of high repute such as Nature, PNAS, Gastroenterology, Journal of Clinical Investigation and Gut.


Thu Nov 23 Systems Medicine Approaches in Clinics 12:00 ‐ 12:15 pm Multi‐omics based strategy to predict graft function and

personalize immunosuppressive therapy in kidney transplantation Nina Babel

Professor Nina Babel is head of the Center for Translational Medicine at the Marien Hospital Herne, Ruhr‐University Bochum and Principal Investigator at Berlin‐Brandenburg Center for Regenerative Therapies, Charité‐Universitätsmedizin Berlin. She studied Human Medicine at the Humboldt‐University in Berlin, where she received her diploma in 1995. She spent her Residence of Internal Medicine at Department of Nephrology and Internal Intensive Care at Charité, specialized in Transplant Medicine and worked as deputy head of Kidney Transplant Outpatient Clinic of Charité, Campus Virchow until 2015. She was recipient of the Rahel Hirsch Habilitation Fellowship and of a Fellowship at the Department Experimental Hematology at Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, USA, and habilitated in 2008 at Charité‐Universitätsmedizin in Berlin. Her prizes and honors include the Young investigator award of American Transplant Physicians, the Young investigator award of International Transplant Society, the Young Investigator Award of European Renal Association, the New key opinion leader of International Transplant Society, TTS, and the Award of European Renal Association.

02:15‐ 02:45 pm Keynote: Pharmacogenomics: from translational research to next

generation benefit‐risk evaluation Julia Stingl

Julia C Stingl (formerly Kirchheiner) M.D. is professor of translational pharmacology at the University Bonn Medical Faculty and head of the research division of the Federal Institute of Drugs and Medical Devices. Since 2014 she is Vice President of the institute. Her research focuses on individualized drug treatment optimized by pharmacogenetics. She developed dose adjustments based on differences in drug clearances caused by pharmacogenetic polymorphisms promoting the way of pharmacogenetics from bench to bedside. She explored genetic influences on drug response and worked on characterization of the physiological role of genetic polymorphisms. She integrated new pharmacogenetic methods such as brain imaging techniques for visualization of pharmacogenetics modulation of individual drug effects. She has more than 190 peer‐reviewed scientific publications, has been cited more than 6200 times with an average citation of 25 per article and an H‐index of 43 (ISI web of science, August 2017).


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Thu Nov 23 Systems Medicine Approaches in Clinics 03:15 ‐ 03:30 pm How to report somatic variants in molecular tumor boards Tim Beißbarth

Tim Beißbarth is leading the Statistical Bioinformatics group at the Department of Medical Statistics of the University Medical Center Göttingen. Tim Beißbarth studied biology and computer science in Cologne, did his PhD in the Theoretical Bioinformatics group at the German Cancer Research Center in 2001 and worked in Berlin, Melbourne (Autralia) and Heidelberg before becoming an associate professor in Göttingen in 2008. The focus of his group is the development of methods and tools to analyse and integrate biomedical data, such as next‐generation sequencing and proteomics data, and to apply these in inderdisciplinary collaboration projects. The group is taking part in several e:Med funded consortia, namely MMML‐Demonstrators, HER2Low, the ELSA consortium Genoperspektiv and the i:DSem consortium MyPathSem. Also, the junior research group of Frank Kramer established through the e:Med MultiPath project originates from the statistical bioinformatics group.

Thu Nov 23 Closing Remarks 03:30 ‐ 03:45 pm Karsten Rippe, Speaker e:Med Project Comittee

Professsor Dr. Karsten Rippe is spokesperson of the e:Med project committee and since April 2007 group leader of the Research Group Genome Organization & Function at the German Cancer Research Center (DKFZ) and the BioQuant in Heidelberg. He is head of the e:Med consortium for systems medicine CancerTelSys, identifying cancer telomere maintenance networks for diagnosis, prognosis, patient stratification and therapy response prediction.


Oral Presentations


Oral Presentations Overview

Tuesday, November 21, 2017

Page Presenting Author Abstract Title

e:Med associations

Satellite Symposium on Technological Innovations

49 Angela Vasaturo

Unraveling the tumor microenvironment architecture by multispectral imaging

50 Philipp Mallm

Follow response to treatment by single-cell sequencing

51 Andreas Schlitzer

Unravelling Cellular heterogeneity - A single cell biology approach

52 Stefan Günther

High resolution single cell analysis in complex adult tissues

Systems Medicine Visionary Talk

57 Uri Alon Design principles of circuits for tissue homeostasis

Technologies in Systems Medicine

61 Benno Schwikowski

Keynote: LEAN analysis biological network hot spots in the age of Big Data

62 Wolfram Gronwald

Metabolomic Changes in Lymphoma in Response to Stromal Stimuli

MMML-Demonstrators

63 Katharina Nekolla

Spatial organization of B cells and T cells predicts loss of renal transplant function SYSIMIT

64 Chris Lawerenz

Introducing the de.NBI Cloud – the novel compute and storage infrastructure for life sciences de.NBI


Overview Oral Presentations

Wednesday, November 22, 2017


e:Med associations

Systems Medicine in European Context

69 Philip Rosenstiel

SYSCID – A systems medicine approach to chronic inflammatory diseases SysINFLAME

70 Bernd Pichler German imaging science in European context Multiscale HCC

71 Markus Löffler

Medical Informatics Initiative and Systems Medicine Initiative CAPSyS

Systems Medicine of Diseases

75 Conor Liston Frontostriatal mechanisms of anhedonia in novel neurophysiological subtypes of depression

76 Julia Krause Metabolomics in Translational Medicine – A Link between Acylcarnitines and Atrial Fibrillation symAtrial

77 Nima Abedpour

Reconstruction of tumor evolution from massively parallel sequencing data SMOOSE, MILES

78 Elisa Espinet

Transcriptomic landscape of Pancreatic Cancer and normal Epithelial and Stromal cells directly isolated from human samples reveals common and cell-type specific deregulated nodes PANC-STRAT

79 Vicente Yépez

Multi-omics analysis methods for the genetic diagnosis of rare diseases mitOmics

Modelling in Systems Medicine

83 Antje Walz Keynote: From Ideas to Medicine – with Modelling and Simulation

84 Dagmar Kulms

Predicting sensitivity of malignant melanoma to combination therapies by network modeling

Melanoma sensitivity

85 Peter-Martin Bruch

A drug - cytokine interaction map for lympho-proliferative disorders SYMPATHY

86 Kathrin Thedieck

Computational modelling of amino acid signaling to kinase networks

MAPTor-NET, GlioPATH

87 Verena Körber Clonal evolution in adult glioblastoma SYS-GLIO

Datenschutzgrundverordnung

90 Boris Reibach Der neue EU-Datenschutz: Folgen für die Forschung

PG Data Security & Ethics


Oral Presentations Overview

Thursday, November 23, 2017


e:Med associations

Systems Medicine Impulse Talks

95 Oliver Kohlbacher

Closing the translational gap – integrating of high-throughput data for personalized cancer treatments into clinical processes iD:Sem

96 Peter Jansen Progressive fibrosis as driving force behind liver cirrhosis, liver failure and hepatocellular carcinoma LiSyM

97 Alfred Pühler The German Network for Bioinformatics Infrastructure de.NBI Helps to Handle Big Data in Life Sciences de.NBI

Systems Medicine Approaches in Clinics

101 Erwin Böttinger

Keynote: Translational approaches for progressive diseases

102 Sylvane Desrivières Updates on the ENIGMA-Epigenetics Working Group

SysMed-Alcoholism

103 Ateequr Rehman

Anti-TNFα restores disrupted metabolic interaction of the intestinal microbiome in IBD SysINFLAME

104 Nina Babel

Multi-omics based strategy to predict graft function and personalize immunosuppressive therapy in kidney transplantation e:Kid

105 Julia Stingl

Keynote: Pharmacogenomics: from translational research to next generation benefit-risk evaluation

106 Mathew Divine

Integrating multi-omics and multi-modality medical imaging to assess hepatocellular carcinoma patient outcome under Sorafenib treatment: A progress report of the Multiscale HCC project Multiscale HCC

107 Ingo Roeder “Systems hematology” – Opportunities, benefits, and limitations HaematoOPT

108 Tim Beißbarth

How to report somatic variants in molecular tumor boards Genoperspektiv


Oral Presentations Satellite Symposium

on Technological Innovations


Satellite Symposium on Technological Innovations Tue, Nov 21, 11:00 am

Unraveling the tumor microenvironment architecture by multispectral imaging Presenting Author: Angela Vasaturo

Integrative Cancer Immunology, Cordeliers Research Center Paris, France

Sponsored by Perkin Elmer The natural history of cancer involves interactions between the tumor and the immune defense mechanism of the host. The crucial role of the patient’s own immune system on clinical outcome is demonstrated by the immunological characterization of the tumor microenvironment. The analysis of type, location and density of tumor infiltrating immune cell components has identified immune cell types that can be either beneficial or harmful to patients showing also that immune cells can infiltrate the core (center) of the tumor and/or remain located in peritumoral areas and that lymphocytic infiltration of tumor or peritumoral tissue can be a favorable prognostic factor in a range of tumor types. In order to better understand the tumor microenvironment and its architecture, recent advances in the field of tissue imaging resulted in the development of multispectral imaging and analysis of up to six immunofluorescence markers within intact tissue sections. This novel technique combines imaging with spectroscopy allowing quantitative assessment of cellular phenotype and activity in a way similar to flow cytometry, while simultaneously providing tissue context and information about cell-to-cell usually difficult or impossible to obtain by other methods. We developed different 7-plex immunofluorescence multispectral panels and applied this novel technology to multiple tumor types in order to identify and quantify the densities of different immune cell subtypes. Furthermore, we have developed an analytical pipeline for first- and second-order spatial analysis of multispectral imaging data, which enables a high-definition characterization of the tumor microenvironment architecture including the spatial distribution of the different immune cell subtypes.


Tue, Nov 21, 11:30 am Satellite Symposium on Technological Innovations

Follow response to treatment by single-cell sequencing Presenting Author: Philipp Mallm

DKFZ Heidelberg

Sponsored by 10x Genomics Cancer can arise in almost any tissue in the human body. Single-cell analysis in cancer may yield insights into the functioning and development of human cells and tissues both in health and diseased conditions. Furthermore, distinct subpopulations may respond differently to treatment and external stimuli, which cannot be detected in bulk sequencing approaches.

During my talk I will present data generated with the 10X Genomics Chromium platform to dissect tumor subpopulations, response to therapeutic intervention and aging processes. 10X Genomics uses the Drop-seq method by encapsulation single cells in oil droplets and capturing RNA molecules on beads with subsequent cDNA synthesis. Workflows from sample to data analysis will be discussed.

With this technique we were for instance able to detect certain gene signatures that may predict the responsiveness to treatment in Multiple Myeloma patients.


Satellite Symposium on Technological Innovations Tue, Nov 21, 12:00 pm

Unravelling cellular heterogeneity - A single cell biology approach Presenting Author: Andreas Schlitzer

University of Bonn

The advent of single cell technologies, such as single cell mRNA sequencing, single cell ATAC sequencing, high dimensional flow cytometry and mass cytometry has allowed to study the organization of the immune system with unprecedented resolution. Myeloid cells are amongst the most heterogeneous cellular entities of the immune system and the current technological advances allow a new, single cell resolution, understanding of these important cell types. The lab, in cooperation with the Platform for Single Cell Transcriptomics and Epigenomics of the German Centre for Neurodegenerative Disease and the University of Bonn (PRECISE), employs a range of single cell biology approaches to understand the complexity of the myeloid cell system during health and disease. Here I will present an integrated single cell biology approach to better understand the development, heterogeneity and functional polarization of human and mouse monocytes, which allows a better, more tailored, clinical use of this important cell type.


Tue, Nov 21, 12:30 pm Satellite Symposium on Technological Innovations

High resolution single cell analysis in complex adult tissues Presenting Author: Stefan Günther Sponsored by WaferGen

Günther S., Yekelchyk M., Salwig I., Preussner J. and Braun T Max-Planck-Institute for Heart- and Lung Research, Bad Nauheim ECCPS Bioinformatics and deep sequencing platform AG Braun Molecular analysis of complex tissues in adult model organisms is a common tool for deciphering processes and networks during development, aging and disease. The majority of such “omic” analyses were done using whole tissue/organs or in macro or micro dissected anatomical regions. However, the complexity and cellular composition of such samples prevent high-resolution analysis. Identification of small subpopulations or specific changes within small cell populations are usually not detected due to massive overrepresentation of signals/data points from bulk cells. To overcome these problems and to gain insights into subpopulation of cells many attempts are being made to switch from bulk analyses to identification of molecular changes in single cells. This approach allows a very high-resolution analysis, but is associated with numerous other problems that have to be resolved to achieve meaningful insights. Our main focus is on the transcriptomics of individual cells and subpopulations. Many techniques and tools were developed during last years to obtain transcriptomics data from hundreds or thousands of cells from different model organisms, organs and tissues. Nonetheless, many experiments require special tissue-dependent conditions limiting the use of standard methods. Here, we show data from 2 projects, which faces special challenges regarding cell size and number of cellular subpopulations within individual samples. In collaboration with Wafergen/Takara Bio we demonstrate that the ICELL8™ Single-Cell System can be used to obtain high-resolution single cell data for particularly large cells or complex cell populations, which are difficult to analyze with other techniques. Our results provide new insights into the heterogeneity of cell populations and the transcriptional networks that regulate biological processes in the corresponding tissues.


Oral Presentations Systems Medicine Visionary Talk


Systems Medicine Visionary Talk Tue, Nov 21, 02:00 pm

Visionary talk: Design principles of circuits for tissue homeostasis Presenting Author: Uri Alon

Weizmann Institute, Israel Tissues maintain a total tissue size that provides desired function, and also maintain the proportions between cells of different types . How this homeostasis of size and composition is maintained is a current research challenge. I will describe progress in understanding which circuits of cells, that communicate by secreted factors, can maintain robust homeostasis. Theory and experiment suggest that the number of possible circuits is small, providing hope that different tissues use similar principles (although with different cell types and molecules). I will also describe how such circuits can be robust to takeover by mutants that mis-read the signals, by means of biphasic responses in which the signal is toxic at both high and low levels (eg glucotoxicity, neuronal excitotoxicity). Just as systems biology identified the recurring circuits inside cells, such as coherent and incoherent feedforward loops, it is possible to foresee a field of tissue-level systems biology, that can provide a language to understand circuits of communicating cells for tissue function and homeostasis.


Oral Presentations Technologies in Systems Medicine


60 e:Med Meeting 2017 on Systems Medicine, Alte Mensa

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